Cross-linked polymeric nanoparticles and metal nanoparticles derived therefrom

ABSTRACT

There are provided internally cross-linked, stable polymeric materials, in the form of substantially spherical particles, each particle consisting essentially of a single macromolecule. They have the unusual property of being soluble or dispersible in a liquid medium without significantly increasing the viscosity of the medium, rendering them potentially useful in imaging applications such as ink jet printers. They can be prepared by dissolving polymeric material in a solvent system to form a solution of the polymeric material at a concentration therein of less than the critical concentration for the polymer, causing the polymeric material to contract into an approximately spheroidal conformation in solution, cross-linking the polymeric material in solution in said spheroidal conformation so assumed, and recovering stable, cross-linked approximately spheroidal polymeric particles from the solution.

FIELD OF THE INVENTION

This invention relates to polymers, and methods for producing polymersof novel structure. More particularly, it relates to a process forcross-linking polymers to produce cross-linked polymers stabilized intoparticularly useful, dense structures. It also relates to novelpolymeric materials having unusual properties.

BACKGROUND OF THE INVENTION

It is known that cross-linking of polymers substantially alters thephysical properties of the polymers. Cross-linking can change athermoplastic polymer to a thermoset polymer, can alter its solubility,density and other physical characteristics. Normally, cross-linking of apolymer is an irreversible process, so that the shape, configuration anddensity of a cross-linked polymer remain substantially permanent oncethe cross-linking process is complete.

A variety of different methods of polymer cross-linking are known. Onemethod is reaction with chemical cross-linking reagents. This isparticularly applicable where the starting polymer is unsaturated(polybutadiene, polyisoprene, styrene-butadiene copolymers, EPDM etc.),so that the groups of unsaturation take part in the cross-linking. Othermethods involve creation of reactive sites such as free radicals on thepolymer chains, e.g. by hydrogen abstraction using a freeradical-generating initiator, by irradiation with V-rays, X-rays, etc.Cross-linking can take place with the polymer in solution in a suitablesolvent, in suspension or in bulk. Cross-linking is normally a randomprocess, which may involve links between different polymer chains andlinks between points on the same polymer chain, and permits only limitedcontrol over its course and extent. In solution and suspension,non-cross-linked polymers tend to adopt an extended, coiledconformation, which is altered in a generally uncontrollable mannerduring cross-linking. There is a need for stable, solid particulatepolymers of predetermined shape, size and density, for use for examplein ink-jet printers, photocopiers and other imaging applications, wherethe achievement of fine definition and resolution of images depends uponthe particle size and uniformity of the particles comprising the imagingmedium, and on the viscosity of the imaging medium.

SUMMARY OF THE INVENTION

The present invention provides a process whereby polymers in solutionare diluted so as effectively to disentangle and isolate the individualmacromolecules from one another in the solution, and then caused tocontract from the normal, random coil conformation to adopt anapproximately spheroidal configuration. Then the macromolecules arestabilized in this conformation, e.g. by applying cross-linkingconditions to the solution, so that the dissolved polymer is internallystabilized in its newly assumed, spheroidal configuration, to formindependent particles stabilized in that conformation. In essence, theparticles are single macromolecules, independent of other, surroundingmacromolecules.

By means of the present invention, dense, spherical particles ofpolymers can be made, having a high degree of uniformity as to particlesize, shape and density. The particle size is largely a function ofmolecular weight of the polymer, a parameter which is controllable byknown methods, during polymerization. Polymers of very narrow molecularweight distribution can be made by known methods of polymerization, andthese will lead to stabilized polymer particles of substantially uniformparticle size, following the method of the present invention. A solutionof the polymer is first prepared using a solvent or mixture of solventsin which the polymer fully dissolves, and at a concentration below thecritical concentration, and caused to contract into a spheroidalconformation. Then the polymer is stabilized, e.g. by cross-linking.Polymer particles of very small size, average diameter in the range0.1–10 nanometers (nanoparticles), can be made in this way.

The resulting polymeric materials are internally cross-linkedmacromolecules, i.e. substantially all of the cross-links are betweengroups on the same polymer chain as opposed to cross-links betweengroups on different polymer chains to bond the polymer chains togetherin a network. These internally cross-linked polymers according to theinvention have solution properties which are quite different from thoseof the same polymeric material either before cross-linking or aftercross-linking in bulk. Conventional high molecular weight polymers(100,000 and higher) have high viscosity in solution, resulting at leastin part from entanglement of and interaction between individualmacromolecules. If such a polymer is cross-linked in the bulk phase, theresulting polymer will not dissolve in any solvent, but may swell whencontacted with solvents. Internally cross-linked materials of theinvention, in contrast, even with molecular weights in excess of1,000,000 can be dispersed in a wide variety of solvents andnon-solvents, but scarcely affect the viscosity of the solution ordispersion at all. This remarkable property makes these new compositionsof the invention of potential utility not only in imaging compositionsas described above, but also in drug delivery applications.

Thus according to one aspect of the present invention, there is provideda process for preparing polymeric material in the form of stablenanoparticles having substantially spherical particulate form, whichcomprises:

-   -   dissolving a polymeric material in a solvent system to form a        solution of the polymeric material at a concentration therein of        less than the critical concentration for the polymeric material;    -   causing the macromolecules of said polymeric material to        contract into an approximately spheroidal conformation in        solution;    -   and stabilizing the polymeric material in solution in said        spheroidal conformation so assumed by creating intra-molecular        bonds.

Stable, intra-molecularly bonded, approximately spheroidal polymericnanoparticles can be recovered from the solution, if desired, bystandard methods.

The term “intra-molecularly bonded” as used herein indicates thepresence of internal cross-links or other bonds linking parts of thesame macromolecule to itself, to the substantial exclusion of bondslinking different macromolecules together (“inter-molecular bonds”).

According to another aspect, the invention provides internallycrosslinked particulate independent macromolecules having substantiallyspheroidal particle shapes, said particles having the ability to bedispersed in a liquid medium without significantly changing theviscosity of the medium.

BRIEF REFERENCE TO THE DRAWINGS

FIG. 1 of the accompanying drawings is a digrammatic illustration of apreferred process according to the invention;

FIG. 2 is an atomic force microscopy picture of one product of Example 1below;

FIG. 3 is an atomic force microscopy picture of another product ofExample 1 below;

FIG. 4 is an atomic force microscopy picture of the product of Example 3below;

FIG. 5 is the UV-visible spectrum of the product of Example 9 below;

FIG. 6 is an electron microscope image, with an enlargement of thecircled portion, of the product of Example 9 below;

FIG. 7 is a curve showing the size distribution of the metal particlesof Example 9 below; and

FIG. 8 is Raman spectra of the polyacrylic acid particles and thepolacrylic acid silver salt particles of Example 9 below.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The process of the present invention is applicable to a wide variety ofpolymeric materials, natural and synthetic. The polymeric materials canbe homopolymers or copolymers of two or more monomers, including blockcopolymers and graft copolymers. It is necessary that the chosenpolymeric material be soluble to a substantial extent in at least onesolvent system, so as to enable it to adopt a contracted spheroidalconformation in solution, as described below.

The chosen polymeric material is first dissolved in an appropriatesolvent system. This may be water, an organic solvent or a mixture oftwo or more such solvents. The polymeric material is dissolved suchthat, in solution individual macromolecules thereof remain distinct,separated and non-entangled with one another. This can be achieved byarranging that the concentration of polymer in solution is below the“critical concentration,” which is the concentration at which theindividual polymer chains in the solution interpenetrate. The separated,non-interpenetrating macromolecules in solution can be condensed e.g. bychanging the solution characteristics, and stabilized by internalcross-linking, to a particle size which, assuming spherical shape, canbe calculated from the molecular weight of the polymer. The ability ofthe macromolecules to achieve a condensed particle size largely inaccordance with theoretical calculations, assuming spheroidal shape,acts as a check or test that the polymer in solution, prior tocondensation and cross-linking, was indeed in the form of independent,separated, non-interpenetrated macromolecules for the initial stages ofthe process of the present invention. A person skilled in the art canreadily conduct such calculations from a knowledge of the chemistry andmolecular weight of the polymer under consideration, and simpleexperiments to determine particle size after stabilization as described.Comparison of this with theoretical calculation and prediction candetermine the critical concentration for the specific polymer solution.

Either as it dissolves (for example in the case of sodium styrenesulfonate-vinyl naphthalene copolymers and similar copolymers), or byreduction of the solvent power of the solution, for example by adding toit a precipitating non-solvent, or a salt which changes the ionizationconditions of the solution, the polymer is caused to condense and tocontract to dense spheroidal structures. Then it is internallystabilized preferably by cross-linking, using a system which iscompatible with the chosen polymer and the chosen solvent system, forexample by exposure to γ-radiation. When each polymer molecule containsthree or more internal cross-links, it can no longer expand to form itsnormal random coil configuration in solution. Instead, it retains itsspheroidal confirmation, the density of which increases with the degreeof cross-linking. In the case of some polymers, e.g. those havingmutually reactive chemical groups such as polypeptides, stabilizationmay occur by reaction of these groups with one another as the polymer iscaused to condense and contract, e.g. by formation of disulphidebridges, without application of a specific cross-linking step.

A wide variety of polymers and copolymers can be used in the presentinvention, provided only that a suitable solvent system is available forthem, and that the random coils can be condensed to denser spheroidalparticles prior to cross-linking. Preferred polymers have ionic charges(polyelectrolytes) so that, in the preferred aqueous solvent systems,the macromolecules are mutually repellant and less likely to agglomerateprior to cross-linking.

Examples of useful polymers in the present invention include polymersand copolymers derived from such monomers as styrene, vinyl naphthalene,styrene sulphonate, vinylnaphthalene sulphonate, acrylic acid,methacrylic acid, methylacrylate, acrylamide, methacrylamide, acrylates,methacrylates, acrylonitrile, N-lower alkyl acrylamides and the like.

One preferred embodiment of the invention involves the use of polymershaving a critical solution temperature, i.e. a temperature below whichthey are soluble in water, and above which they are insoluble in water.Using the process of the present invention, such polymers can bedissolved in water, caused to assume a condensed, spheroidalconformation and internally cross-linked as described. They can then beused for delivery and controlled release of other organic compounds suchas drugs. The drug can be dispersed in a suspension of the cross-linkedpolymer at a temperature above the critical solution temperature, atwhich the drug will be absorbed by the polymer in itscollapsed-particulate form. When the temperature is reduced below thecritical solution temperature, the polymer particle swells and slowlyreleases the drug. Polymers having critical solution temperaturesinclude polymers of N-isopropylacrylamide (NIPAM), the critical solutiontemperature of which can be adjusted by copolymerization with othermonomers.

FIG. 1 of the accompanying drawings diagrammatically illustrates aprocess according to an embodiment of the invention. At stage 1, thepolymer exists in a concentrated solution, in which the macromoleculechains 10 are intertwined and interpenetrated, so that any attempt tocross-link them at this stage would cause inter-reaction between thepolymer chains.

Upon dilution of the solution, stage 2, below the criticalconcentration, the polymer macromolecules 10 are spaced apart from oneanother, but still in their random coil configuration. Upon reducing thesolvent power of the solvent system, e.g. by introducing a non-solventor a salt, the macromolecules condense, stage 3, into generallyspherical conformation 12, and can now be cross-linked, eg. byapplication of ionizing radiation, at stage 4, whereupon internalcross-linking, as opposed to inter-macromolecular cross-linking occurs,effectively locking the macromolecules into the configurations assumedin stage 3. Then the cross-linked, approximately spherical macromoleculeparticles can be recovered e.g. by freeze drying, for use inapplications referred to above.

When the macromolecule particles are re-dissolved e.g. in water, theyhave very little, if any, effect on the viscosity of the solvent (in anyevent less than a 10% resulting increase in the viscosity). This is dueto the fact that the macromolecules do not agglomerate to anysignificant extent, nor do they expand or mutually interact to anysignificant extent. This unusual property renders the nanoparticlesuseful in a number of specialty applications. The nanoparticlemacromolecules having critical solution temperature as described aboveare, fro example, especially useful as drug carriers, where drugs areassociated with the polymers in solution and delivered to very smallveins and capillaries of the body, e.g. certain areas of the brain,which are so small that they cannot be penetrated by drug solutions ofother than very low viscosity.

Whilst water is the preferred solvent for use in the present invention,other polar solvents can also be used if desired, alone or in mixtureswith each other and in admixture with water. The best choice of solventdepends to a large extent on the choice of polymer. Polar solvents suchas lower alkanols, ketones, amines, dimethylsulfoxide and the like aresuitable alternatives to water, when working with a polymer of limitedsolubility in water.

Another aspect of the present invention comprises the use of internallycross-linked macromolecules as described above in the preparation ofnanoparticles of metals, i.e. metal particles which are substantiallyspherical in shape, and which have an average diameter in the range0.1–10 nanometers, preferably from 0.1–8 nanometers and more preferablyfrom 0.1–5 nanometers. Such nanoparticles of metals comprise anotheraspect of the invention. This process aspect uses internallycross-linked polymers as described above, in which the polymer is apolyelectrolye such as polyacrylic acid or a salt thereof e.g. sodiumpolyacrylate. For example, by dissolving them in water containing alarge excess of ferrous ions, the sodium ions can be replaced by ferrousions. After removal of the sodium ions, the particles can be heated inair or oxygen to above 200–300° C. The polymer content is largelyremoved by pyrolysis, leaving extremely small particles of iron oxidewith very large surface area and important electrical and catalyticproperties. If the process is carried out in a reducing atmosphere, highsurface metal particles can be obtained. Other metal salts such assilver salts (silver nitrate for example), copper salts and gold saltscan be used to produce finely divided metal particles useful in imagingand, because of their very high surface area, in catalysis. Palladium,platinum, titanium and molybdenum are examples of metals which can beprepared in nanoparticle form according to the present invention, foruse in catalysis. Substantially any metal which is stable in itsmetallic form and which has a water soluble salt can be used in thisway. The metal salt can be dialyzed against the sodium polyacrylate (orsimilar polymeric salt) particles of the invention, to remove the alkalimetal and replace it with the other metal. Then the product is reduced,e.g. by application of laser radiation, and solid metal nanoparticlese.g. silver particles, in some cases surrounded by a fine layer ofresidual polymer which has a stabilizing effect, are obtained.

In another modification, ionic groups on internally cross-linkedpolymers of the present invention, for example the sodium acrylategroups in the particles made in examples 1, 2 and 8 below, can easily beconverted to other useful functional groups. Sodium acrylate groups forexample can be converted converted to the corresponding acid chloride bytreatment with thionyl chloride. Dye molecules containing reactivehydroxyl or amino groups can then be permanently bound to both thesurface and the interior of the particles giving rise to products usefulin imaging applications such as in inkjet printing.

The invention is further described with reference to the followingspecific illustrative examples.

EXAMPLE 1 Internally Cross-Linked Polyacrylic Acid

The sodium salt of poly(acrylic) acid (Polysciences Inc. Cat #18755), ofmolecular weight of 1,300,000, was used in a cross-linking processaccording to the invention. 97 mg of polymer was dissolved in 100 ml ofdistilled water. After solution was complete the pH was 8.2, and 98 mgof sodium chloride was slowly added to cause the polymer particles tocontract. 5 cc. of the solution was flushed with nitrogen, sealed in aglass vial, and irradiated with 10 megarad of Co⁶⁰ γ radiation. Afterradiation the vial was opened and the solution dialysed against waterfor 5 days to remove the salt, and the polymer particles recovered byfreeze drying under vacuum. The particles were studied by atomic forcemicroscopy (A.F.M) (film cast onto mica, to produce tapping mode AFMheight image) and shown to be perfectly spherical, with diameters of 6to 10 nanometers (see FIG. 2). No such particles were observed in theuncross-linked control sample. The particles observed are close to thesize calculated for a completely collapsed macromolecular chain ofmolecular weight one million. When dispersed in water at a concentrationof 1%, the solution had a viscosity virtually the same as pure water. Atthe same concentration a water solution of uncross-linked startingmaterial was much more viscous.

The procedure was repeated with a polyacrylic acid (sodium salt) ofmolecular weight about 700,000, and the A.F.M. picture of this productis presented as FIG. 3 hereto. The spherical shape of the particles isclearly apparent from this picture. The scale on the Figure is inmillimicrons. The particles have a diameter of approximately 4nanometers (0.4 millimicrons).

EXAMPLE 2

The procedure of Example 1 was repeated except that before addition ofthe sodium chloride the pH of the solution was reduced to 3.2 byaddition of small amounts of 0.1 N hydrochloric acid. After addition ofsodium chloride and cross-linking with 10 megarad of γ-rays,nanoparticles of the same size (6–10 nanometers) were observed as inExample 1 by A.F.M.

EXAMPLE 3

Copolymers of sodium styrene sulfonate and vinyl naphthalene containingabout equal quantities of each comonomer are known to form hypercoiledpseudomicellar conformations in water, i.e. they do not form expandedrandom coils, but are collapsed into much smaller spherical structureswith much higher coil density due to the hydrophobic interactionsbetween the naphthalene groups and water. These particles are negativelycharged due to the ionization of the styrene sulfonate groups in water.The polymers can also be internally cross-linked by the followingprocedure. A polymer containing 50% by weight sodium styrene sulfonateand 50% of vinyl naphthalene was prepared in benzene solution AIBN ascatalyst. After isolation and purification by dialysis against purewater it had a molecular weight M_(w) of 200,000.

100 mg of this polymer was dissolved in 100 ml distilled water and afterpurging with oxygen-free nitrogen was irradiated with a dose of 0.40megarad of Cobalt⁶⁰ γ-rays. A.F.M. analysis of the resulting particlesshowed spherical particles with an average diameter of 7.5 nanometers.The A.F.M. picture of the particles is presented as FIG. 4 hereof. A 1%solution of these particles in water showed very little increase overthat of water itself.

EXAMPLE 4

Internal cross-linking can be carried out by other means besides yradiation. In some cases, irradiation of the aqueous dispersion withhigh intensity U.V. laser light will cause internal cross-linking. Asimpler procedure is to prepare a copolymer with a small number ofdouble bonds which can be connected by vinyl polymerization. In thisexample a copolymer of 50% styrene sulfonate and 48% vinyl naphthaleneand 2% divinyl benzene was prepared as in Example 3. 100 mg of thispolymer was dissolved in 100 ml of water to which was slowly added withstirring 1.0 cc of benzene containing 4 mg styrene and 1 mg of AIBN(azobis-iso-butyryl nitrile). After purging with nitrogen 2 cc of thismixture was heated to 70° C. for 5 hours with stirring. After isolationand purification by dialysis spherical nanoparticles were observed byA.F.M.

EXAMPLE 5

An additional 2 cc of the solution prepared in Example 4 was shaken witha small amount of styrene monomer and allowed to separate. Excessstyrene was removed and the polymer was internally cross-linked byexposure of the solution to near ultraviolet light (λ=313 nm from theAmerican Ultraviolet Irradiation System for 1 hour. After isolation andpurification cross-linked nanoparticles with the viscosity properties ofthe γ irradiated materials from Example 1 and 2 were produced.

EXAMPLE 6

Poly N-isopropyl acrylamide (NIPAM) is an important polymer which isoften used in drug delivery systems. It has a lower critical solutiontemperature (LCST) of 31° C. It is soluble in water below thistemperature but precipitates sharply above this. This temperature can belowered by copolymerization with hydrophobic monomers such asacrylonitrile and raised by hydrophilic monomers such as acrylamide.These co-polymers can be internally cross-linked by any of theprocedures described above. In a specific example 100 mg of polyNIPAMwith a molecular weight of 200,000 g/mole was dissolved in 100 ml waterat 20° C. and was cross-linked with 10 megarads of γ radiation. Afterisolation and purification, the internally cross-linked 5–10 nmnanoparticles can be used for the controlled delivery of other organiccompounds. For example the drug can be absorbed by the collapsedparticle in a water dispersion above LCST. After removal of theunabsorbed drug, the dispersion will remain stable until the temperatureof the water is reduced below LCST, at which point the particle swellsand slowly releases the drug. Since the size of the internallycross-linked nanoparticle is extremely small (˜10 nm) it can accessalmost any part of the human body including the smallest bloodcapillaries which makes it of interest in a variety of medicaltherapies. The delivery polymers can also be made sensitive to pHinstead of temperature.

EXAMPLE 7

Polymers such as NIPAM, polyacrylamide and polyethylene oxide, which donot contain ionized groups, are difficult to keep separate in watersolution while the cross-linking process is taking place. This reducesthe yield and purify of the desired internally cross-linkednanoparticles. Cleaner products and higher conversions can be achievedby including an ionizable comonomer. A copolymer of 2% acrylic acid and98% NIPAM was prepared. At a pH of about 8–9 in water most of theacrylic acid units will be ionized, thus giving a strong negative chargeto each polymer molecule. At high dilution, this prevents theagglomeration of individual chains to form larger particles. 100 mg ofthis polymer was internally cross-linked by the procedure of Example 6.A.F.M. studies of the internally crosslinked particles showed a muchlower concentration of larger agglomerated particles than those preparedin Example 6.

EXAMPLE 8

A solution of sodium polyacrylate was prepared as in Example 1, andafter the addition of sodium chloride, 4 mg of 4,4′-diazidostilbene-2,2′sodium sulfite dissolved in 1 cc benzene was added slowly withcontinuous stirring. After flushing with nitrogen, the ampoule wassealed and irradiated for 1 hour with 313 nm U.V. light in the AmericanUltraviolet Irradiation system. After irradiation the product wasisolated by freeze drying and purified by dialysis as in Example 1.A.F.M. measurements showed particles similar to those found in Example1.

EXAMPLE 9 Nanoparticles of Metal

Nanoparticles of polyacrylic acid sodium salt prepared according toExample 1 were dialysed against dilute hydrochloric acid to remove thesodium ions, and then treated with excess silver nitrate in aqueoussolution to form the silver salt of the acrylic acid groups in thepolymer particles. Irradiation of these particles in aqueous dispersionwith γ-radiation (10 Mrad) gave a dark orange solution. The UV-visiblespectrum shown in FIG. 5 shows peaks corresponding to the well-knownsurface plasmon of silver colloids of size smaller than the wavelengthof light, indicating that the silver ions have been reduced to metallicsilver. The silver colloids are much more stable than those reported inthe literature, as indicated by the fact that the plasmon band intensitydid not change for many weeks after preparation.

After isolation of the particles and drying of them, spherical particlesof diameter about 5 nm were observed by AFM. An electron microscopeexamination (TEM), FIG. 6, shows that the spherical silver particles aresurrounded by a hazy region believed to be unreacted polymer, a possiblefactor in the enhanced stability of the silver nanoparticles.

The average diameter of the reduced silver particles was 3.5±0.53 nm.The diameter of the exterior, including the hazy region, was 5.2±0.8 nm.The particle size distribution is shown on FIG. 7.

Similar results were obtained by irradiation of the original saltparticles with an intense laser pulse from a picosecond quadrupledNd:YAG laser or XeF excimer laser, and by a chemical reducing agent suchas sodium in liquid ammonia.

Similar experiments with iron and copper salts gave similar results,with aqueous solutions giving rise to various colours, depending uponthe size of the particles.

Further evidence of encapsulated particles is shown on FIG. 8, Ramanspectra, showing the surface enhanced Raman effect of silvernanoparticles on poly acrylic acid, PAA. In the absence of the reducedmetal, the Raman peaks for pure polyacrylic acid are hardly discernible,but after the silver salt is reduced to metallic silver, strong enhancedRaman peaks are observable. This is strong evidence for theencapsulation of the silver particles by the remaining polymer from theoriginal particle. This coating can be easily removed by washing with asuitable solvent, or by heating to 300° C. or higher in a reducingatmosphere.

EXAMPLE 10 Larger Particles

Larger particles of polyacrylic acid salts and other polymers for thepreparation of metal particles by the process of the invention can bemade by emulsion polymerization in the absence of surfactant, by themethod of O'Callaghan et. al, Journal of Applied Plymer Science, Vol 58,2047–2055 (1995). This paper describes a method of making monodispersepolymer latices with sizes of 40 nm and higher.

By following the procedure of this paper, there was prepared a copolymerof butyl acrylate (30%) with acrylic acid (70%), cross-linked with 3%divinylbenzene. The average size of these particles was 230±20 nm.Treatment with silver nitrate as in Example 9 followed by laserirradiation with the Nd:YAG laser while stirring the aqueous dispersiongave silver containing nanoparticles about 200 nm in diameter.

1. A method of making an internally cross-linked single polymer moleculehaving a size of from about 0.1 to about 10 nm comprising: (a) providinga polymer molecule; (b) causing said polymer molecule to condense toform a condensed single polymer molecule; and (c) internallycross-linking said condensed single polymer molecule to form saidcross-linked single polymer molecule.
 2. The method of claim 1, whereinsaid cross-linked single polymer molecule is substantially spherical. 3.A method of making a metal particle having a size of from about 0.1 toabout 10 nm comprising: (a) providing an internally cross-linked singlepolymer molecule; (b) contacting said single polymer molecule with ametal salt to incorporate said metal salt into said single polymermolecule; (c) causing said metal salt incorporated in said singlepolymer molecule to form a metal particle having a size of from about0.1 to about 10 nm.
 4. The method of claim 3, wherein step (c) comprisesheating the single polymer molecule having the metal salt incorporatedtherein.
 5. The method of claim 4, wherein said heating removes saidpolymer by pyrolosis.
 6. The method of claim 4, wherein said heating isconducted in a reducing atmosphere.
 7. The method of claim 3, whereinstep (c) comprises irradiating the single polymer molecule having themetal salt incorporated therein.
 8. The method of claim 7 wherein theirradiation comprises T irradiation.
 9. Internally cross-linked,particulate, single polymer molecules having substantially spheroidalparticle shapes, said particles having the ability to be dispersed in aliquid medium without significantly changing the viscosity of themedium, said macromolecular particles further comprising apolyelectrolyte.
 10. An internally cross-linked single polymer moleculehaving a size of from about 0.1 to about 10 nm, wherein the polymer is apolymer or copolymer derived from a monomer or monomers selected fromthe group consisting of styrene, vinyl naphthalene, styrene sulphonate,acrylic acid, methacrylic acid, acrylate, methacrylate, acrylamide,methacrylamide and acrylonitrile.
 11. An internally cross-linked singlepolymer molecule having a size of from about 0.1 to about 10 nm, furthercomprising a metal or metal salt.
 12. An internally cross-linked singlepolymer molecule having a size of from about 0.1 to about 10 nm.
 13. Thecross-linked single polymer molecule of claim 10, wherein saidacrylamide comprises an N-loweralkyl acrylamide.
 14. The cross-linkedsingle polymer molecule of claim 11, wherein said metal or metal salt isselected from the group consisting of silver, iron, copper, gold,palladium, platinum, titanium and molybdenum or a salt thereof.